CD8 T cells drive anorexia, dysbiosis, and blooms of a commensal with immunosuppressive potential after viral infection

Proc Natl Acad Sci U S A. 2020 Oct 6;117(40):24998-25007. doi: 10.1073/pnas.2003656117. Epub 2020 Sep 21.


Infections elicit immune adaptations to enable pathogen resistance and/or tolerance and are associated with compositional shifts of the intestinal microbiome. However, a comprehensive understanding of how infections with pathogens that exhibit distinct capability to spread and/or persist differentially change the microbiome, the underlying mechanisms, and the relative contribution of individual commensal species to immune cell adaptations is still lacking. Here, we discovered that mouse infection with a fast-spreading and persistent (but not a slow-spreading acute) isolate of lymphocytic choriomeningitis virus induced large-scale microbiome shifts characterized by increased Verrucomicrobia and reduced Firmicute/Bacteroidetes ratio. Remarkably, the most profound microbiome changes occurred transiently after infection with the fast-spreading persistent isolate, were uncoupled from sustained viral loads, and were instead largely caused by CD8 T cell responses and/or CD8 T cell-induced anorexia. Among the taxa enriched by infection with the fast-spreading virus, Akkermansia muciniphila, broadly regarded as a beneficial commensal, bloomed upon starvation and in a CD8 T cell-dependent manner. Strikingly, oral administration of A. muciniphila suppressed selected effector features of CD8 T cells in the context of both infections. Our findings define unique microbiome differences after chronic versus acute viral infections and identify CD8 T cell responses and downstream anorexia as driver mechanisms of microbial dysbiosis after infection with a fast-spreading virus. Our data also highlight potential context-dependent effects of probiotics and suggest a model in which changes in host behavior and downstream microbiome dysbiosis may constitute a previously unrecognized negative feedback loop that contributes to CD8 T cell adaptations after infections with fast-spreading and/or persistent pathogens.

Keywords: Akkermansia; CD8 T cell; LCMV; anorexia; microbiome.

MeSH terms

  • Akkermansia
  • Animals
  • Anorexia / immunology*
  • Anorexia / microbiology
  • Anorexia / virology
  • CD8 Antigens / immunology*
  • CD8 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / microbiology
  • Dysbiosis / immunology
  • Dysbiosis / microbiology
  • Dysbiosis / virology
  • Firmicutes / immunology
  • Firmicutes / metabolism
  • Gastrointestinal Microbiome / immunology
  • Humans
  • Immunologic Memory / immunology*
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic Choriomeningitis / microbiology
  • Lymphocytic Choriomeningitis / pathology
  • Lymphocytic choriomeningitis virus / pathogenicity
  • Mice
  • T-Lymphocytes / immunology
  • T-Lymphocytes / microbiology
  • Verrucomicrobia / immunology
  • Verrucomicrobia / pathogenicity
  • Virus Diseases / immunology*
  • Virus Diseases / microbiology
  • Virus Diseases / pathology


  • CD8 Antigens

Supplementary concepts

  • Akkermansia muciniphila